Micropipetter, especially for the discharge of a sample and a diluent

ABSTRACT

A manually operable or automatically actuated micropipetter for the delivery of precise quantities of a sample liquid and a quantity of a dilution liquid, comprising a barrel receiving two coaxial pistons including a small-diameter piston for delivering the sample and a large-diameter piston carrying the smalldiameter piston and operable to deliver a dilution liquid or a liquid medium capable of flushing the discharge passage to eliminate traces of a previous sample therefrom and enabling the uptake of a new sample. The two-liquid arrangement provides a body of the dilution or rinsing liquid behind the sample so that no compressible space is formed between the port of the device and the pistons or plungers. The small piston or plunger, carried by the large piston or plunger, may be displaced independently thereof in the axial direction and means is provided for the bodily displacement of the large-diameter plunger for drawing the dilution or rinsing liquid into the system and for incrementally displacing the large-diameter plunger in the opposite direction for discharging incremental quantities of dilution or rinsing liquid.

United States Patent [191 Buchler et a].

Gross, Bergenfield, both of N..l.; Bernard Parker, Westport, Conn.

[73] Assignee: Buchler Instruments Division Nuclear-Chicago, NJ.

[22] Filed: Mar. 30, I973 [2]] App]. No.: 346,637

[52} US. Cl. 222/309 [5 I] Int. Cl. GOlf 11/06 [58] Field of Search 73/4256, 425.4 P; 23/253,

[56] References Cited UNITED STATES PATENTS 3,646 8l7 3/l972 Hinchman et al. I. 73/4256 Primary Examiner-Stanley H. Tollberg Attorney, Agent, or Firm-Karl F. Ross; Herbert Dubno May 13, 1975 57 ABSTRACT A manually operable or automatically actuated micropipetter for the delivery of precise quantities of a sample liquid and a quantity of a dilution liquid, comprising a barrel receiving two coaxial pistons including a small-diameter piston for delivering the sample and a large-diameter piston carrying the small-diameter piston and operable to deliver a dilution liquid or a liquid medium capable of flushing the discharge passage to eliminate traces of a previous sample therefrom and enabling the uptake of a new sample The two-liquid arrangement provides a body of the dilution or rinsing liquid behind the sample so that no compressible space is formed between the port of the device and the pistons or plungers The small piston or plunger, carried by the large piston or plunger, may be displaced independently thereof in the axial direction and means is provided for the bodily displacement of the large-diameter plunger for drawing the dilution or rinsing liquid into the system and for incrementally displacing the large-diameter plunger in the opposite direction for discharging incremental quantities of dilution or rinsing liquid.

15 Claims, 8 Drawing Figures PATENTEI] HAY I 3 i375 SHEH 2 OF 3 PATENIEDKAY 1 31975 3883.044

SHEET 3 BF 3 FIG. 7 mar 62 FIG. 8

MICROPIPETTER, ESPECIALLY FOR THE DISCHARGE OF A SAMPLE AND A DILUENT FIELD OF THE INVENTION Our present invention relates to a micropipetter system and, more particularly, a system for accepting small samples and discharging these samples with great precision.

BACKGROUND OF THE INVENTION In laboratory work generally and in chemical. biological and biochemical analysis, in biochemical technology. in the preparation oflarge numbers of cultures and other tasks requiring the removal of precise quantities or aliquots of a sample or a specimen liquid and/or the delivery of precise quantities of a liquid to a receptacle or the like, micropipetters are employed in a variety of constructions. Of special interest are micropipetters having a generally cylindrical barrel, a calibrated plunger and a small-caliber tube. passage or duct (tip) adapted to be immersed in the sample liquid for induction of the sample into the tube and adapted to be disposed above the mouth of a vessel for discharge of the sample previously taken up. Mechanism is generally provided to adjust the limit of the stroke of the piston or plunger so that the quantity of liquid taken up and dispensed can be established with more or less great precision and high reproducibility These systems have the disadvantage that the reproducibility and precision are affected by numerous factors. including the compressibility of a gas space between the plunger and the body of sample liquid induced into the passage.

Mention may also be made of pipette systems in which, generally from some external source, a quantity of some diluting liquid or rinsing liquid is caused to flow through the pipette passage to remove traces of the delivered sample before the pipette is again employed in the induction operation. Systems of the latter type have been expensive, difficult to construct and use. and of inconvenient size and configuration. Frequently. the induction and discharge of the sample are characterized by inaccuracy and variability for the reasons previously stated. in spite of the use of the diluting or rinsing liquid.

OBJECTS OF THE INVENTION The object of the present invention is to provide an improved micropipetter system whereby the aforementioned disadvantages are obviated.

It is another object of the invention to provide a sampling device adapted to take up and dispense small vol umes of a sample with considerable precision and reproducibility.

Yet a further object of the invention is to provide a device of the character described whereby all ofa dispensed sample is ejected from the delivery passage into the receptacle. Another object of the invention is the provision of a micropipetter which can accurately meter at diluting liquid into a receptacle. after or with delivery of the sample.

Yet another object of the invention is the provision ot'a samplcndiluter which can be employed with a minimum of effort. is adaptable to manual and machine or automatic use, is of low cost and high capacity and accuracy. and is suitable for use with corrosive, toxic. contaminating and noxious materials which have not successfully been handled by many precision pipettes heretofore.

SUMMARY OF THE INVENTION These objects and others which will become apparent are attained, in accordance with the present invention, by providing a micropipetter having a generally cylindrical barrel open at one end thereof and formed at the other end with a small-caliber passage through which liquid may be induced into a chamber of the barrel at this latter end and may be discharged therefrom.

The barrel receives a large-diameter plunger or piston which is axially shiftable within the barrel, and defines with the aforementioned first end thereof, a compartment which is always filled with liquid during operation of the device so that there is a continuum of liquid between the inlet port and this plunger, free from compressible space (i.e. entrapped gas). A second smalldiameter plunger or piston is mounted in the large diameter plunger and is axially shift-able therein to induce the sample into the passage and discharge the sample therefrom. actuating means being provided for this small-diameter piston or plunger capable of being operated independently of the principal plunger.

According to an important feature of the invention, the actuating mechanism includes a threaded spindle extending within the large plunger and a nut arrangement in the large-diameter plunger for releasable cngagement with this threaded spindle, thereby enabling the plunger to be axially shifted within the barrel along the spindle to fill the compartment with a dilution liquid.

According to yet another feature of the invention. the actuating means includes an angularly and axially shiftable member connected by a unidirectional clutch to one of the relatively rotatable threaded members which advance the system so that one of the pistons is axially shifted upon angular displacement ofthis handle while the other is axially shifted with axial displacement of the handlev It has been found to be advantageous to provide the threaded spindle in rotatable entrainment with the driven member of the clutch so that, when the handle coupled with the driving member of the clutch is m tated, the spindle is rotated and the large plunger is axially displaced incrementally to drive the diluting or rinsing liquid from the system. The handle may be coupled directly to the small-diameter piston so that, when the handle is axially shifted in one direction, the smalldiameter piston is drawn away from the passage and. when the handle is displaced axially in the other direction, the small-diameter piston is advanced toward the passage.

At the end of the barrel remote from the compartment, adjustable stop means is provided for limiting the stroke of the handle and. therefore the small-diameter piston, so that the quantity of sample which is induced into the passage may be carefully regulated. It has been found to be advantageous to constitute the smalldiameter piston as a needle passing through the largediameter plunger via an O-ring seal and extending into the passage with sufficient clearance to enable the di luting or rinsing liquid to be forced past the needle through the passage.

The barrel remote from the passage is formed with an arcuate throughgoing slot portion through which the handle or arm passes. and an axially extending slot por tion at one of the ends of the arcuate slot portion along which the handle can be shifted for alternately taking up and dispensing the sample.

According to yet another feature of the invention, the barrel is bipartite and has a glass portion defining the compartment and provided with the passage, and a synthetic-resin portion affixed to the glass portion by a flange coupling tightened with the threaded ring or other coupling mechanism. This allows the mechanism to be primarily received in the synthetic portion and facilitates rapid replacement of the glass portion which comes into contact with the diluting liquid and the sample, thereby permitting a noncontaminated member to replace the contaminated member. The glass portion also allows the compartment to be viewed for detection of entrapped gases.

According to another feature of this invention, the synthetie-resin portion remote from the outlet is formed with an axially extending slot through which an arm of the large-diameter piston extends for axial displacement of the latter, the arm engaging the threaded member (i.e. the nut) of the large-diameter piston for biasing it radially away from the threaded spindle against a spring to release the large-diameter plunger for axial displacement relative to the threaded spindle.

The clutch, according to the invention, comprises a disk having fibers along a face thereof oriented direc tionally and cooperating with a wire-mesh disk forming the other clutch member so that rotation is only permitted in one direction (i.e. the sense in which the fibers extend from their anchored end to the free end.

The end of the barrel forming the chamber can be provided. according to the invention, with a tip or the like to which replacement tips or tubules can be af fixed. especially when the replacement tips are composed of throwaway synthetic-resin materials and the pipette tip is tapered to receive the tapered mouth of the throw away tip. The barrel is preferably transparent so that the condition of the liquid can be readily discerned and the absence of gas noted. When gas develops or is inadvertently trapped in the system, the gas may be displaced by using conventional syringe procedures. It will be appreciated that, especially when a thin or small-caliber tube is attached to a disposable tip, the volume of the tube must always exceed the volume to be dispensed and taken up so that the sample liquid never enters the chamber of the syringe body which remains filled with the diluent liquid and therefore never mixes therewith.

It will be appreciated that, since the small plunger need not be closely filled into the syringe passage into which it can extend, it operates only by displacement into and out of the large piston. Thus no valves nor stopcocks are required with the system of the present invention.

DESCRIPTION OF THE DRAWING The above and other objects, features and advantages of the present invention will become more readily apparent from the following description. reference being made to the accompanying drawing in which:

FIG. I is an axial cross-sectional view through a micropipetter for manual operation, according to the present invention;

FIG. 2 is a cross-sectional view taken along the line Il-ll of FIG. I;

FIG. 3 is a cross-sectional view taken along the line Ill-III of FIG. 1;

FIG. 4 is a cross-sectional view taken along the line lV-IV of FIG. 1;

FIG. 5 is an elevational view of a portion of the barrel of the device of FIG. I rotated through from the position illustrated in the latter Figure;

FIG. 6 is a cross-sectional view along the line VI-VI of FIG. 1 with the actuating arm thereof in a dispensing position;

FIG. 7 is a fragmentary elevational view, partly broken away ofa modification of the system in FIG. I; and

FIG. 8 is an axial cross-sectional view of a detail of an adjusting means and system of the type shown in FIG. I.

SPECIFIC DESCRIPTION In the drawing we have shown a micropipetter which comprises a barrel or syringe-like body 1 composed of a material inert to attack by the liquids processed and preferably of a transparent material, e.g. glass or a polyacrylate at least at the dispensing end la of this barrel. At the dispensing end, there is provided a tip 2, here shown to be composed of metal and threaded into the synthetic-resin barrel. Of course, where the tip is composed of glass as shown at 102 in FIG. 7, it may receive replaceable tapered tips which can be discarded after each use or after a particular series of uses.

In the embodiment of FIG. I, however, the sample delivery tip 3 is shown to be composed of synthetic resin, glass or other material and maybe fitted onto the slightly tapered spigot portion 4 of the tip 2. A right angle construction has been illustrated for the delivery tip 3, although it should be understood that a straightline tip may also be used, that the fitting 2 may accept LUER-lock syringe needles, and that substantially any dispensing tip or tube arrangement may be employed, provided that a gas-tight seal is maintained with the syringelike body or barrel of the device.

The barrel I is formed with a generally cylindrical bore 5 terminating at the dispensing end la in a conically convergent wall 6 which preferably has the same taper as the forward end 7 of a main plunger 8 composed of a material, such as polytetrafluoroethylene, generally inert to the liquids dispensed. The cylindrical wall of bore 5, the end face 6 of the bore and the leading face 7 of the plunger or piston 8 define a chamber 9 which is filled with a diluent or rinsing liquid as will be apparent hereinafter.

The plunger or piston 8 is, as illustrated, generally cylindrical and is formed with an outwardly open groove 10 receiving a sealing ring ll of rubber or some other elastomeric material inert to the diluent liquid and sealing the diluent piston 8 against the wall of the barrel 1.

The diluent piston 8 is formed with a central bore 11 receiving a threaded spindle 12 the latter being tubular to accommodate a cylindrical rod 13 forming the body of the sampling and dispensing piston 14. The rod 13 terminates at its end turned toward the passage 15 of the barrel I, in a needle 16 which can extend with clearance into this passage 15. A O ring or like seal I7 is provided between the needle 16 of the chamber piston and the diluent piston 8.

The diluent piston 8 is formed with a radially open chamber 18 which receives a radially shiftable stud 19, the latter being connected to a half nut 20 which is biased by a conical spring 21 in the direction of arrow A.

The stud 19 passes through an axially extending slot 22 formed in the barrel beyond the maximum rearward position of the seal 10.

The diluent piston 8 is shown in its extreme right hand postion to be seated against a spring ring 23 lodged in an inwardly opening groove 24 in the wall of bore 5. Between the ring 23 and another similar ring 25, there is provided a unidirectional clutch arrangement, generally represented at 26 and including a driven clutch member 27, a driving clutch member 28 and unidirectional means 29 and 30 respectively connected to the driving and driven members. The unidirectional means may include an oriented-fiber disk confronting a wire-mesh screen so that the screen can only entrain the fiber-carrying disk when it is moved in a direction away from the free ends of the fibers, but slips relative to the fiber disk in the opposite sense.

The driven member 28 of the clutch is provided with a guide pin 29 which passes through an axially extending bore 30 of a radial arm 31 having a knob 32 at the free end thereof to facilitate displacement by the user.

The arm 31 is connected to a cylindrical body 53 axially receiving the end 54 of rod 13 opposite the needle 16. In an extreme rightward position of this cylindrical body 53, it abuts a set screw 34 adjustably threaded into a disk 35 which is received between a pair of spring rings 36 and 37 and closes the otherwise open end of the barrel 1.

The arm 31 projects radially from the barrel through an L-shaped slot, the leg 39 of which extends in the circumferential direction and terminates at one end thereof in an axial slot portion 40. In other words. at the end of slot 40 turned toward the dispensing tip, the arm 31 can be swung angularly as represented by the arrow B and back, and at the end of slot 39 can be shifted along slot 40 in the axial direction represented by arrow C and in the reverse direction (arrow D). FIG. 6 shows the position of the arm in solid lines as it is axially shiftable along slot 40 and in dot-dash lines as it has been swung along slot 39.

In FIG. 7, we show an arrangement wherein the dispensing portion 101:: of the barrel 101 is formed from glass, as is especially advantageous when pyridine and like noxious materials are to be used as the diluent, the glass member having an outwardly extending flange l0lb which abuts a threaded boss [01c of the synthetic-resin portion 101d housing the mechanism. A nut l0le of polytetrafluorethylene detachably connects the glass and polyacrylate portions of the barrel.

In operation, assuming the diluent piston 8 in an extreme left-hand position in which the frustoconical end 7 of the diluent piston sits against the frustoconical wall 6 of bore 5, stud 19 (refill knob) is pressed radially inwardly (arrow E), thereby disengaging the half nut 20 from the threaded spindle 12. The diluent 8 is then shifted in the direction of arrow F and, assuming that the tip 3 is immersed in a vessel containing the diluent, liquid is drawn up into chamber 9. Of course, the barrel 1 may then be tilted upwardly, the gas bubbles. if present. caused to collect in the passage 15, and expelled by a forward displacement of the diluent piston 8 in accordance with normal syringe techniques. Liquid may then be expelled from chamber 9 until the delivery tip 3, the passage 15 and the chamber 9 are all filled with liquid and, if the tip 3 is again immersed in the vessel, the diluent piston can be brought to rest against ring 23 to insure a continuum of liquid in tip 3, passage 15 and chamber 9.

The tip 3 may then be inserted into a vessel containing the sample liquid whereupon the handle or arm 31 is swung in a clockwise sense (FIG. 6) along the slot portion 39 into its extreme clockwise position and is shifted to the right (FIGS. 1 and 5) along the slot 40. The arm draws the rod 13 and pin 16 to the right, thereby inducing liquid to flow upwardly into the tip 3 in a quantity determined by the excursion of arm 3] and piston 14, i.e. to the limit established by the adjusting screw 34.

The tip 3 is withdrawn from the sample-liquid vessel and positioned at the desired location for sample discharge, e.g. a sample receiving vessel, whereupon the arm 31 is shifted in the direction of arrow D, i.e. to the left (FIGS. 1 and 5) along the slot 40. This advances the rod 14 and needle 16 of the sample piston to drive the sample liquid (e.g. about 10 microliters) from the tip 3. Thereupon the arm 31 is swung in the counterclockwise sense (FIG. 6) along slot 39 (arrow B) so that the members of clutch 26 are entrained to rotate the spindle 12 and advance the piston 8. The movement of this piston to the left (FIG. 6) discharges a portion (e.g. about 30 microliters) of the rinsing or diluent liquid in compartment 9, the diluent flowing through passage 15 and the tip 3 to flush any trace of sample therefrom. Since the tip 3 and chamber 9 and the passage connecting same are always filled with a contin uum of liquid, no compressible air space is provided. When only a predetermined amount of diluent liquid is to be dispensed, the arm 31 need merely be shifted to the desired degree as represented by the calibrations 39 along the slot 39. The calibrations 39 and any stop for the angular displacement of the arm 31, of course, constitute means for adjusting the angular stroke of the arm to obtain the desired displacement of rinsing fluid.

When the diluent or rinsing fluid has been discharged, the sample and dispensing steps can then be repeated as described. When all of the rinsing liquid is discharged, of course, the piston 8 will again be shifted to the right (by depression of stud 19) to draw additional rinsing liquid into the chamber. Between successive sampling and dispensing steps, the tip may be changed, in which case, prior to sampling, a portion of the diluent liquid can be driven into the tip by several angular oscillations of arm 31 along the slot 39. This ensures the aforementioned continuum of liquid.

In FIG. 8, we show a system in which the stroke of arm 31, rod 14 and needle 16 can be adjusted. In this embodiment, a threaded rod 60 is received in a threaded disk 61 fitted to the rear end of the cylinder 62 and held in place by a spring ring 63 and a retaining ring 64, the latter likewise being held by a spring ring 65. The retaining ring 64 holds the flange foot 66 of a cylindrical member 67 against the ring 61, the member 67 being provided with a plug 68 having a slot 69 whereby the plug, locked to the screw 60, can be rotated by a screwdriver inserted through the open end 70 of the tubular member 67, the body 68 is formed with a circumferential indicator groove 71 receiving a red-pigmented strand which moves along a flat 72 portion, in the inner wall of tubular member 67 and calibrated to represent volumetric displacements of the sample piston 14, 16. The tubular member 67 may of course be removed for attachment of the implement to a mechanism for reciprocating the sample piston and angularly displacing same when the system is to operate automatically.

We claim:

1. A pipetter comprising:

a housing having a port and defining a compartment communicating with said port;

a first piston shiftable in said housing for varying the volume of said compartment;

a second piston shiftablc in said housing for varying the volume of said compartment independently of said first piston;

actuating means movable relatively to said housing and operatively connected to said second piston for displacing same relative to said housing; and

mechanism operatively connecting said first piston to said actuating means for incremental displacement of said first piston subsequent to displacement of said second piston whereby discharge of a sample by movement of said second piston is followed by incremental discharge of a quantity of liquid from said compartment by said first piston. said housing being a barrel forming a cylinder defining said compartment at one end, said first piston being axially shiftable in said cylinder and said second piston is axially shiftable in said first piston. said actuating means including an arm connected to said second piston and projecting laterally from said barrel for axially shifting said second piston relative to said first piston and said barrel.

2. The pipetter defined in claim 1 wherein said mechanism further comprises a threaded spindle extending axially in said first piston and connected with said clutch. a nut on said first piston threadedly engaging said spindle. and means for disengaging said nut from said spindle to permit axial displacement of said first piston independently of said spindle.

3. The pipetter defined in claim 2 wherein said nut is a halfnut said mechanism further comprising a spring urging said halfnut radially into engagement with said spindle, and a stud projecting radially from said barrel and said first piston and engaging said halfnut for depressing same against the force of said spring.

4. The pipetter defined in claim 3, further comprising an axially extending slot receiving said stud, said stud being displacable along said slot upon disengagement of said halfnut from said spindle.

5. The pipetter defined in claim 2 wherein said clutch comprises a driving disk operatively connectable to said arm and a driven disk operatively connectable to said spindle. one of said disks being provided with a layer of oriented fibers and the other disks being provided with a discontinuous surface engageable with aid layer of fibers for mutual entrainment of said disks upon rotation in one sense but for mutual sliding of said surfaces in the opposite sense.

6. The pipetter defined in claim 2 wherein said second piston extends axially through said spindle, further comprising a sealing ring carried by said first piston and engaging the wall of said cylinder at an end of said first piston proximal to said compartment. and a sealing ring on said first piston engaging said second piston.

7. The pipetter defined in claim 2 further comprising adjustable means in said barrel axially engaging said second piston for defining the excursion thereof.

8. The epipetter defined in claim 4 wherein the last mentioned means includes calibrations for setting the excursion of said second piston.

9. The pipetter defined in claim 1 wherein said barrel comprises a first barrel member composed of glass and defining said compartment, a second barrel portion alignable with said first barrel portion, and means for axially detachably interconnecting said barrel portion.

10. The pipetter defined in claim 1 wherein said first piston is composed of polytetrafluoroethylene.

ll. The pipetter defined in claim 1, further comprising means for adjusting the excursion of said second piston and means for adjusting the advance of said first piston.

12. The pipetter defined in claim 1 wherein said barrel, at least in the region of said compartment is transparent to permit detection of gas trapped therein.

13. The pipetter defined in claim I wherein said port is formed with means enabling replaceable tips to be mounted thereon.

14. A pipetter comprising:

a housing having a port and defining a compartment communicating with said port;

a first piston shiftable in said housing for varying the volume of said compartment;

a second piston shiftable in said housing for varying the volume of said compartment independently of said first piston;

actuating means movable relatively to said housing and operatively connected to said second piston for displacing same relative to said housing; and

mechanism operatively connecting said first piston to said actuating means for incremental displacement of said first piston subsequent to displacement of said second piston whereby discharge of a sample by movement of said second piston is followed by incremental discharge of a quantity of liquid from said compartment by said first piston, said housing being a barrel forming a cylinder defining said compartment at one end. said first piston being axially shiftable in said cylinder and said second piston is axially shiftable in said first piston, said actuating means including means connected to said second piston for axially shifting same relative to said first piston and said barrel. said barrel being transparent at least at said end thereof to permit viewing of gas increments in liquid contained in said compartment, said barrel being formed at said port with means accommodating replacement tips for induction and discharge of sample liquid, said first piston being generally elongated and composed of polytetrafluorethylene and being formed at a locataion adjacent said compartment with a first angular seal engaging the wall of said cylinder. said first piston being further formed with an axially extending central bore. said second piston including a rod extending axially in said central bore of said first piston and provided with a needle extending axially into said compartment through said end of said first piston, said pipetter further comprising a second sealing ring on said first piston engaging said needle. said actuating means including an arm con nected to said rod at an end thereof opposite said one end of said barrel and extending radially from said barrel said barrel being formed with an L' shaped slot having an axially extending slot portion and a circumferentially extending slot portion receiving said arm, said other end of said barrel being formed with calibrated adjusting means limiting the axial excursion of said rod. said mechanism including a clutch having a driving disk, a driven disk and oriented-fiber surface means for coupling said disks for joint rotation in one sense and decoupling them upon rotation in the opposite sense. said arm being connected to said driving disk. said mecha nism including a threaded spindle bore of said first piston, a halfnut threadedly engaging said spindle. a spring radially urging said halfnut into engagement with said spindle. and a stud projecting radially from said barrel and connected to said halfnut for depressing same out of engagement with said spindle, said barrel being formed with an axially extending slot receiving said stud and preventing rotation of said first piston 15. A valveless syringe, comprising an elongated reservoir having a tube adapted to communicate with a vessel;; 21 first piston body displaceable in said ehammber for drawing a quantity of a first liquid into said chamber; a second piston body displaceable on said first body in said chamber for drawing a second liquid through said tube immediately behind said first liquid and means for displacing at least one of said bodies to discharge said second fluid from said tube by ejection of a portion of said first fluid from said reservoir. said means including respective members connected to each of said piston bodies and projecting laterally from said reservoir through respective slots formed therein for actuation of the piston bodies. 

1. A pipetter comprising: a housing having a port and defining a compartment communicating with said port; a first piston shiftable in said housing for varying the volume of said compartment; a second piston shiftable in said housing for varying the volume of said compartment independently of said first piston; actuating means movable relatively to said housing and operatively connected to said second piston for displacing same relative to said housing; and mechanism operatively connecting said first piston to said actuating means for incremental displacement of said first piston subsequent to displacement of said second piston whereby discharge of a sample by movement of said second piston is followed by incremental discharge of a quantity of liquid from said compartment by said first piston, said housing being a barrel forming a cylinder defining said compartment at one end, said first piston being axially shiftable in said cylinder and said second piston is axially shiftable in said first piston, said actuating means including an arm connected to said second piston and projecting laterally from said barrel for axially shifting said second piston relative to said first piston and said barrel.
 2. The pipetter defined in claim 1 wherein said mechanism further comprises a threaded spindle extending axially in said first piston and connected with said clutch, a nut on said first piston threadedly engaging said spindle, and means for disengaging said nut from said spindle to permit axial displacement of said first piston independently of said spindle.
 3. The pipetter defined in claim 2 wherein said nut is a halfnut, said mechanism further comprising a spring urging said halfnut radially into engagement with said spindle, and a stud projecting radially from said barrel and said first piston and engaging said halfnut for depressing same against the force of said spring.
 4. The pipetter defined in claim 3, further comprising an axially extending slot receiving said stud, said sTud being displacable along said slot upon disengagement of said halfnut from said spindle.
 5. The pipetter defined in claim 2 wherein said clutch comprises a driving disk operatively connectable to said arm and a driven disk operatively connectable to said spindle, one of said disks being provided with a layer of oriented fibers and the other disks being provided with a discontinuous surface engageable with aid layer of fibers for mutual entrainment of said disks upon rotation in one sense but for mutual sliding of said surfaces in the opposite sense.
 6. The pipetter defined in claim 2 wherein said second piston extends axially through said spindle, further comprising a sealing ring carried by said first piston and engaging the wall of said cylinder at an end of said first piston proximal to said compartment, and a sealing ring on said first piston engaging said second piston.
 7. The pipetter defined in claim 2 further comprising adjustable means in said barrel axially engaging said second piston for defining the excursion thereof.
 8. The epipetter defined in claim 4 wherein the last mentioned means includes calibrations for setting the excursion of said second piston.
 9. The pipetter defined in claim 1 wherein said barrel comprises a first barrel member composed of glass and defining said compartment, a second barrel portion alignable with said first barrel portion, and means for axially detachably interconnecting said barrel portion.
 10. The pipetter defined in claim 1 wherein said first piston is composed of polytetrafluoroethylene.
 11. The pipetter defined in claim 1, further comprising means for adjusting the excursion of said second piston and means for adjusting the advance of said first piston.
 12. The pipetter defined in claim 1 wherein said barrel, at least in the region of said compartment is transparent to permit detection of gas trapped therein.
 13. The pipetter defined in claim 1 wherein said port is formed with means enabling replaceable tips to be mounted thereon.
 14. A pipetter comprising: a housing having a port and defining a compartment communicating with said port; a first piston shiftable in said housing for varying the volume of said compartment; a second piston shiftable in said housing for varying the volume of said compartment independently of said first piston; actuating means movable relatively to said housing and operatively connected to said second piston for displacing same relative to said housing; and mechanism operatively connecting said first piston to said actuating means for incremental displacement of said first piston subsequent to displacement of said second piston whereby discharge of a sample by movement of said second piston is followed by incremental discharge of a quantity of liquid from said compartment by said first piston, said housing being a barrel forming a cylinder defining said compartment at one end, said first piston being axially shiftable in said cylinder and said second piston is axially shiftable in said first piston, said actuating means including means connected to said second piston for axially shifting same relative to said first piston and said barrel, said barrel being transparent at least at said end thereof to permit viewing of gas increments in liquid contained in said compartment, said barrel being formed at said port with means accommodating replacement tips for induction and discharge of sample liquid, said first piston being generally elongated and composed of polytetrafluorethylene and being formed at a locataion adjacent said compartment with a first angular seal engaging the wall of said cylinder, said first piston being further formed with an axially extending central bore, said second piston including a rod extending axially in said central bore of said first piston and provided with a needle extending axially into said compartment through said end of said first piston, said pipetter further comprising a second sealing ring on said first piston engaging said needle, said actuating means including an arm connected to said rod at an end thereof opposite said one end of said barrel and extending radially from said barrel, said barrel being formed with an L-shaped slot having an axially extending slot portion and a circumferentially extending slot portion receiving said arm, said other end of said barrel being formed with calibrated adjusting means limiting the axial excursion of said rod, said mechanism including a clutch having a driving disk, a driven disk and oriented-fiber surface means for coupling said disks for joint rotation in one sense and decoupling them upon rotation in the opposite sense, said arm being connected to said driving disk, said mechanism including a threaded spindle bore of said first piston, a halfnut threadedly engaging said spindle, a spring radially urging said halfnut into engagement with said spindle, and a stud projecting radially from said barrel and connected to said halfnut for depressing same out of engagement with said spindle, said barrel being formed with an axially extending slot receiving said stud and preventing rotation of said first piston.
 15. A valveless syringe, comprising an elongated reservoir having a tube adapted to communicate with a vessel;; a first piston body displaceable in said chammber for drawing a quantity of a first liquid into said chamber; a second piston body displaceable on said first body in said chamber for drawing a second liquid through said tube immediately behind said first liquid and means for displacing at least one of said bodies to discharge said second fluid from said tube by ejection of a portion of said first fluid from said reservoir, said means including respective members connected to each of said piston bodies and projecting laterally from said reservoir through respective slots formed therein for actuation of the piston bodies. 